POS0144 NOVEL ANTIBODY BIOMARKERS THAT PREDICT FAILURE TO ACHIEVE EARLY AND SUSTAINED DISEASE REMISSION OR LOW DISEASE ACTIVITY AFTER INTENSIVE FIRST-LINE THERAPY IN RHEUMATOID ARTHRITIS
Authors: P. Vandormael, A. Pues, E. Sleurs, J. Liesenborgs, P. Verschueren, V. Somers
Journal: Annals of the Rheumatic Diseases (2022)

Background Current EULAR guidelines for the management of rheumatoid arthritis (RA) recommend the use of classical synthetic disease-modifying anti-rheumatic drugs (csDMARDs), combined with short-term use of glucocorticoids (GC) as first-line therapy. Still, finding out which patients will show a poor response to such intensive first-line therapy is currently based on trial and error. Therefore, we recently performed a screening for novel antibody biomarkers that could predict the lack of response to csDMARD/GC combination therapy, resulting in identification of antibodies to 6 novel University Hasselt (UH)-RA antigens. Objectives The aim of this study was to validate these novel antibody biomarkers for their potential to identify at baseline, which RA patients fail to reach remission (rem-), or low disease activity (LDA), after intensive csDMARD therapy. Methods Presence of antibodies to the identified UH-RA antigens was measured using ELISA in 179 baseline samples from participants of the CareRA trial, which evaluated the efficacy of different first-line combination therapies 1 . Baseline antibody reactivity was correlated with remission or LDA, over a two-year follow-up period, according to the Disease Activity Score based on 28 joints with C-reactive protein (DAS28CRP), the DAS28 with erythrocyte sedimentation rate (DAS28ESR), and the clinical/simplified disease activity index (CDAI/SDAI). Results Baseline antibody reactivity against a panel of 3 antigens was higher in patients failing to reach DAS28CRP (31 vs 15%, p=0.007) or DAS28ESR (30 vs 14%, p=0.007) remission at week 8, or those failing to reach SDAI (36 vs 17%, p=0.018) or CDAI (37 vs 17%, p= 0.01) LDA at week 8, compared to RA patients that did reach these respective disease states. Baseline antibody reactivity correlated with lack of DAS28CRP remission after 8, 16, 40 and 52 weeks of first-line therapy, and was present in one in three DAS28CRP rem- patients, and in one in two DAS28CRP rem- patients that were seronegative for RF and ACPA. For each of the remission criteria studied (DAS28CRP, DAS28ESR, SDAI and CDAI), baseline antibody reactivity against these antigens was significantly higher in RA patients that did not maintain sustained remission (resp. 25 vs 12%, p=0.029; 24 vs 11%, p=0.041; 24 vs 4%, p=0.009; 24 vs 4%, 0.011), or sustained LDA (resp. 29 vs 13%, p=0.007; 27 vs 11%, p=0.008; 29 vs 14%, p=0.018; 29 vs 14%, p=0.013) between week 8 and week 52, compared to patients that did reach these respective disease states. Conclusion We have identified a set of 3 antibody biomarkers that predict the failure to achieve early and sustained remission and LDA in response to intensive first-line RA therapy. Therefore, the presence of these antibodies might indicate the need for another first-line treatment option in a personalized medicine approach. References [1]Stouten V, Westhovens R, Pazmino S, De Cock D, Van der Elst K, Joly J, Verschueren P; CareRA study group. (2019) Effectiveness of different combinations of DMARDs and glucocorticoid bridging in early rheumatoid arthritis: two-year results of CareRA. Rheumatology (Oxford ). 58(12):2284-2294. Disclosure of Interests Patrick Vandormael: None declared, Astrid Pues: None declared, Ellen Sleurs: None declared, Jori Liesenborgs: None declared, Patrick Verschueren Speakers bureau: Eli Lilly, MSD, Galapagos, Roularta, Consultant of: Galapagos, Gilead, Pfizer, Sidekick Health, Eli Lilly, Nordic Pharma, ABBVIE, Celltrion, BMS, UCB, Grant/research support from: Holder of the Pfizer Chair Management of Early Rheumatoid Arthritis at KU Leuven, Veerle Somers Grant/research support from: research grant from Pfizer.